Comparison of 5-fluorouracil alone, 5-fluorouracil with levamisole, and 5-fluorouracil with hepatic irradiation in the treatment of patients with residual, nonmeasurable, intra-abdominal metastasis after undergoing resection for colorectal carcinoma.

BACKGROUND: The authors conducted a randomized Phase III trial of three treatment regimens for patients with residual, nonmeasurable, intra-abdominal metastatic disease after undergoing resection for primary colorectal carcinoma. METHODS: To be eligible for this study, patients had to be both free of other malignancies and capable of starting their therapy within 3-6 weeks after surgery. They were required to have an Eastern Cooperative Oncology Group performance status < 3; to be chemotherapy, radiation, and immunotherapy naïve; to have adequate bone marrow, renal, and hepatic function; and to provide written, informed consent. The patients were divided into two cohorts: patients with no demonstrable hepatic metastasis (Group A) and patients with hepatic metastasis (Group B). RESULTS: The 229 patients in Group A were randomized to receive either 5-fluorouracil (5-FU) (n = 116 patients) or 5-FU with levamisole (n = 113 patients). The median survival (15.4 months and 15.3 months, respectively, for Groups A and B) was virtually identical. The two groups also were similar in terms of time to treatment progression, which was 7.9 months for group that received 5-FU alone 7.7 months for the group that received levamisole with 5-FU. The 168 patients in Group B with hepatic metastasis underwent a three-way randomization: 5-FU alone (n = 60 patients), 5-FU with levamisole (n = 54 patients), and 5-FU with hepatic irradiation (n = 54 patients). The median overall survival for the three treatment arms were similar, with 17.3 months for the group that received 5-FU alone, 16 months for the group that received 5-FU with levamisole, and 14.4 months for the group that received hepatic irradiation in addition to 5-FU: The time to treatment failure was 6.7 months, 6.8 months, and 8.3 months, respectively, for the three groups. The toxicity experienced by patients was as expected with the regimens, and no differences were observed between any of the treatment groups. The primary toxicities were hematologic and gastrointestinal. There was one treatment-related death due to adult respiratory distress syndrome, which occurred on the first day of the fourth cycle of 5-FU and levamisole. Other Grade 4 toxicities included nine patients with Grade 4 leukopenia, one patient with Grade 4 sepsis, and one patient with Grade 4 gastrointestinal toxicity, including blood loss and diarrhea. CONCLUSIONS: This study showed no treatment advantage for any of the combined modalities over 5-FU alone in this group of patients with intra-abdominal, nonmeasurable disease.

Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: ten-year analysis--an intergroup study.

PURPOSE: Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients. This report updates the analysis of the high-risk group and reports the results of the low-risk group. METHODS: Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured > or = 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy. RESULTS: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group (P=.0006 for DFS and P=.02 for OS). Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51 % (P=.0009) and OS of 75% versus 65% (P=.06). Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group. CONCLUSION: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free state and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group.

A long-term analysis of 620 patients with malignant melanoma at a major referral center.

BACKGROUND: A univariate and multivariate statistical analysis of a single surgeon's experience with resectable malignant melanoma during 26 years (November 1970 to August 1996) was conducted. METHODS: Six hundred twenty consecutive patients were registered. Univariate analysis of disease-free survival (DFS) and melanoma survival (MS) was calculated by the Kaplan-Meier method and correlated to American Joint Committee on Cancer stage, thickness, ulceration, site, lymph node involvement, age, sex, type, and excision margins. Linear trends, log-rank test, and pairwise comparisons were used to discriminate differences in survival curves. A Cox proportional hazards model was used for multivariate analysis and determination of relative risk. RESULTS: Univariate analysis of stage, thickness (in millimeters), ulceration, lymph node involvement, age, type, and margins of excision were predictive of DFS (5 years, 85.7%; 10 years, 82.5%) and MS (5 years, 92.2%; 10 years, 87.8%) (P < .01). Multivariate analysis revealed correlations with thickness, ulceration, and age in predicting DFS (relative risk = 2.75, 2.21, and 1.47, respectively) and MS (relative risk = 2.66, 2.47, and 1.48, respectively). The 5-year MS rate was 73.3% and 93.3% for patients with positive and negative lymph nodes, respectively. Of 133 patients who underwent lymph node dissection, 28 (21.1%) had nodal metastases. Patients with primary melanomas thicker than 4 mm had 50% metastatic involvement of their lymph nodes. CONCLUSIONS: Our findings reveal that thickness, ulceration, and age are the most important predicting factors in DFS and MS. The data support including ulceration and age in modifying American Joint Committee on Cancer staging for melanoma.

The National Cancer Data Base report on gastric carcinoma.

BACKGROUND: The National Cancer Data Base (NCDB) represents a national electronic registry system now encompassing almost 60% of incident cancers in the United States. In combination with other programs of the American College of Surgeons Commission on Cancer, the NCDB offers a working example of voluntary, accurate, and cost-effective "outcomes management" on a both a local and a national scale. METHODS: For the accession years 1985-1993, the NCDB has obtained information on demographics, patterns of care, disease stage, treatment, and outcome for a convenience sample of 57,407 gastric carcinoma cases (1.6% of total NCDB cases). In addition to describing trends, this report focuses on 5-year relative survival for a cohort of 1987-1988 cases staged according to the third edition of the American Joint Committee on Cancer's TNM classification, as well as patterns of care for a cohort of 1992-1993 cases. RESULTS: Stage-stratified 5-year relative survival for the 1987-1988 cohort was as follows: IA, 71%; IB, 56%; II, 37%; IIIA, 18%; IIIB, 11%; IV, 5%. Without noteworthy changes in stage distribution, demographics, or other factors, the proportion of patients treated by total gastrectomy is increasing slightly, but proximal gastrectomy for proximal cancers remains surprisingly popular. The proportion of cases receiving postoperative adjuvant treatment has declined slightly. Presumably because of advanced age and/or medical infirmity, a substantial proportion of U.S. patients with disease at every stage receive no treatment for cancer. CONCLUSIONS: This analysis of patterns of care has revealed unexplained variations in treatment and opportunities for improvement. Treatment of the elderly, infirm patient with gastric carcinoma appears problematic.

Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an Eastern Cooperative Oncology Group study.

PURPOSE: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. METHODS AND MATERIALS: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. RESULTS: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. CONCLUSION: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm.

Squamous cell carcinoma of the breast: a clinical approach.

BACKGROUND: Squamous cell carcinoma (SCC) of the breast is rare. It remains unclear whether a "pure" form of SCC exists or if all known cases actually represent an extreme form of squamous metaplasia within adenocarcinoma. Due to its rarity and controversy over its definition, there are no good data on appropriate management and prognosis. METHODS: All cases of breast carcinoma indexed at our institution were reviewed to identify seven cases where squamous metaplasia was a significant component of the pathologic diagnosis. Slides and electron micrographs were reviewed by a single pathologist. Clinical information was obtained from medical records. RESULTS: These cases support the concept of a disease continuum with varying degrees of squamous metaplasia. When tumors identified as "pure" SCC on light microscopy are subjected to ultrastructural analysis, either separate squamous and glandular cells are present or both histologic features are noted to coexist in the same cell. CONCLUSIONS: Identification of "pure" cases of SCC appears clinically unimportant. All patients presented with advanced disease, thus necessitating aggressive management regardless of histology. Mastectomy was performed due to large tumor size and adjuvant chemotherapy given rather than hormones because of receptor negativity. The mixed histology should direct future drug choice. The role of radiation remains unclear.

Phase II trial of etoposide, doxorubicin, and cisplatin combination in advanced measurable gastric cancer. An Eastern Cooperative Oncology Group study.

A phase II study was performed to determine the efficacy and toxicity of the etoposide, doxorubicin, cisplatin (EAP) regimen in the treatment of patients with advanced measurable gastric cancer in a multi-institutional cooperative group setting. Thirty-one evaluable patients with advanced measurable gastric adenocarcinoma were treated with etoposide 120 mg/m2 on days 3, 4, and 5, doxorubicin 20 mg/m2 on days 1 and 8, and cisplatin 40 mg/m2 on days 2 and 9. The treatment was repeated every 28 days. Objective responses were seen in 7 (23%) patients, all achieving partial remissions. Median survival was 9 months for the entire group. Toxicity was mostly hematologic, with grade 3 leukopenia in 26% and grade 4 leukopenia in 55% of the patients. There were 4 treatment-related deaths that were attributable to severe leukopenia and sepsis. Because of the high toxicity and moderate response rate, this regimen is not superior to other less toxic regimens and cannot be recommended for the treatment of advanced gastric cancer outside of an investigational protocol.

Barriers to clinical trials. Part III: Knowledge and attitudes of health care providers.

The role of clinical trials is becoming extremely important for our understanding of the effects of different therapeutic modalities of cancer treatment and the value of their interactions. Participation of patients in clinical trials remains disappointingly low, with less than 3% of the estimated 1.17 million patients with newly diagnosed cancers entering the studies. Several physician-based factors hinder accrual of patients--(1) lack of awareness of or access to clinical trials, (2) physician bias that the trial therapy is not as good as the "standard therapy" even though the standard therapy may provide a response rate of less than 20%, (3) physician's concern about losing patients to follow-up, (4) the complexity of the clinical trial(s), which requires excessive amount of time to discuss, implement, and follow-up the patient, (5) the lack of equitable compensation for the physician's time and effort, and (6) excessive costs of laboratory and radiologic tests that are not paid by the agency or group sponsoring the study, particularly in Phase I and II trials. These factors are confounded by the lack of institutional review boards in several community hospitals, associated with a complex and lengthy procedure to institute such a board. The article presents recent surveys dealing with attitudes and practices of health care providers toward clinical trials. The National Cancer Institute, the American Cancer Society, and other societies, groups, and agencies, including the health insurance industry, should continue to encourage and support clinical trials.

Prognostic factors in early breast carcinoma.

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)

Hormonal treatment for metastatic breast cancer. An Eastern Cooperative Oncology Group Phase III trial comparing aminoglutethimide to tamoxifen.

BACKGROUND: Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness. METHODS: Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual. RESULTS: There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable. CONCLUSIONS: Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies.

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.

PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.

Endoscopic laser therapy for obstructing and/or bleeding colorectal carcinoma.

The primary role of the neodymium yttrium aluminum garnet (Nd:YAG) laser has been to relieve obstruction and to control hemorrhage associated with malignant neoplasms throughout the gastrointestinal tract. In an initial series (IS), the authors demonstrated the efficacy of the Nd:YAG laser as initial preresectional therapy (PR) in 11 patients with obstructing and resectable left colonic or rectal tumors obviating initial operative diversion and allowing for primary resection and anastomosis. In addition, the authors have illustrated the benefit of the Nd:YAG laser in relieving obstruction and arresting bleeding in those patients with either widely metastatic or nonresectable (NR) locoregional disease. Their cumulative experience from 1985 to the present includes 53 patients (PR: 29 and NR: 24). In the PR group, 25 lesions were above the peritoneal reflection and 4 below. Twenty-five patients underwent low anterior resection and four abdominoperineal resection. In the NR group, 17 patients were treated for imminent obstruction and 7 for bleeding. Ten lesions were above and 14 below the peritoneal reflection. There was one laser-related complication in the series (1.8%). There was no significant morbidity or mortality in the PR group. The reduction in length of stay (LOS) and total hospital costs (THC), when compared to the IS has continued to be significant. Laser therapy for those patients in the NR groups is a safe and acceptable alternative to permanent colostomy with its accompanying morbidity and mortality.

HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.

PURPOSE: Amplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease. PATIENTS AND METHODS: Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) after surgery. RESULTS: The rate of HER-2/neu overexpression was 14.3% in all tumors combined and was higher in invasive carcinomas with (21.5%) than without (11.2%) a significant noninvasive or in situ histologic component (P less than .0001). There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy (n = 453). Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and/or the presence of noninvasive carcinoma, we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component (n = 179). Patients of this group with HER-2/neu-positive tumors showed only 40% disease-free survival (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative tumors (P less than .0001). A similar inverse correlation was observed between overexpression and overall survival in the same group of patients (P = .0001). In a separate analysis involving patients receiving adjuvant chemotherapy, those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION: Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.

Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients.

PURPOSE: Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF). PATIENTS AND METHODS: All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years. RESULTS: Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012). CONCLUSION: S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node-negative breast cancer patients with small, ER-positive tumors.

Prognostic potential of DNA flow cytometry measurements in node-negative breast cancer patients: preliminary analysis of an intergroup study (INT 0076).

An ancillary study (INT 0076) to the Intergroup clinical trial of node-negative breast cancer patients (INT 0011) was performed to retrospectively evaluate DNA flow cytometry measurements of ploidy (DNA content) and proliferative capacity (S-phase fraction) for their ability to predict time to recurrence. Of the 915 patients eligible for the clinical trial, 788 were registered for the ancillary flow cytometry study (INT 0076). Four hundred and three of these patients [estrogen receptor (ER)-positive, tumor size less than 3 cm] had been registered to the observation arm of the clinical trial and 385 (ER-negative and/or tumor size greater than or equal to 3 cm) had been randomly assigned to adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone for six cycles) or to observation. Paraffin blocks from 95% (748 of 788) of these patients were obtained, 712 of which had sufficient cancer tissue to be evaluable for the flow cytometric assay. DNA ploidy status (DNA diploid vs DNA aneuploid) was evaluable for 565 (79%) specimens, 64% of which were aneuploid. Proliferative capacity was estimated by the percentage of cells having an S-phase DNA content, using a trapezoidal modeling algorithm(s) as previously described. The median S-phase value for the entire group (both registered and randomly assigned patients) was 6.97%, which defined the cutoff for interpretation of high or low S-phase values. With a median follow-up time of 4.55 years, S-phase fraction, but not ploidy status, is a significant predictor for time to recurrence in both the randomly assigned and the untreated population (observed registered group and observed randomly assigned group).(ABSTRACT TRUNCATED AT 250 WORDS)

Chemotherapy versus observation in high-risk node-negative breast cancer patients.

Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial.

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.

Short-term tamoxifen plus chemotherapy: superior results in node-positive breast cancer.

Three hundred eleven patients with node-positive breast cancer were randomized to one of three adjuvant treatments: cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil; all of the above with tamoxifen citrate; or all of the above with tamoxifen and bacillus Calmette-Guerin vaccination. Local therapy for all patients was a modified radical mastectomy. Estrogen receptors were measured on all primary tumors. Patients were stratified by the number of positive nodes (one to three nodes and more than three nodes) and estrogen-receptor value (less than 3 femtomole/mg and greater than or equal to 3 femtomole/mg). Follow-up is available, with a mean of 9.1 and maximum of 14.2 years. In this study the efficacy of short-term tamoxifen is apparent over that of chemoimmunotherapy alone and continues to be significant with prolonged follow-up. The addition of tamoxifen to chemoimmunotherapy significantly prolonged disease-free survival among patients with estrogen receptor-positive tumors who were postmenopausal, who had larger tumors (greater than 3 cm), or who had more extensive axillary node involvement (more than three nodes). Tamoxifen improved overall survival for patients with estrogen receptor-positive tumors larger than 3 cm. The addition of bacillus Calmette-Guerin Cytoxan, methotrexate, 5-fluorouracil, and tamoxifen did not significantly alter disease-free or overall survival.

The role of pre-resectional laser recanalization for obstructing carcinomas of the colon and rectum.

The Nd:YAG laser has proved its efficacy for recanalizing obstructing lesions throughout the gastrointestinal tract. In a preliminary report using the Nd:YAG laser as a pre-resectional treatment for functionally obstructing colorectal carcinoma we showed that this modality accomplished good decompression, allowing for formal bowel preparation, a definitive one-stage operation with no increased mortality or morbidity, and that the use of the Nd:YAG laser was significantly cost-effective. Our cumulative experience from 1985 to 1988 includes 11 patients; nine underwent pre-resection laser therapy followed by primary resection and anastomosis, and two underwent abdominoperineal resection. Tumors were located above the peritoneal reflection in nine patients and below in two patients. All patients had orthograde bowel preparation with Golytley the day after laser therapy and underwent definitive surgery. There were no wound or intra-abdominal infections or postoperative fatalities. These 11 laser-treated patients were compared with age-matched controls who had undergone earlier colonic diversion. No significant differences were noted for age, sex, tumor location or differentiation, stage, or overall survival. Comparisons between laser-treated patients and controls for the preoperative length of stay and total length of stay were significantly different (p = 0.002 and p = 0.001, respectively). When comparing laser-treated patients and controls, preoperative and total hospital costs were significantly different (p = 0.003 and p = 0.01). We have found that pre-resectional laser recanalization has allowed for primary resection and anastomosis in patients who have obstructing left colon and rectal carcinomas without compromising patient safety.